The Emotional Brain as a Predictor and Amplifier of Chronic Pain.

Human neuroimaging studies and complementary animal experiments now identify the gross elements of the brain involved in the chronification of pain. We briefly review these advances in relation to somatic and orofacial persistent pain conditions. First, we emphasize the importance of reverse translational research for understanding chronic pain-that is, the power of deriving hypotheses directly from human brain imaging of clinical conditions that can be invasively and mechanistically studied in animal models. We then review recent findings demonstrating the importance of the emotional brain (i.e., the corticolimbic system) in the modulation of acute pain and in the prediction and amplification of chronic pain, contrasting this evidence with recent findings regarding the role of central sensitization in pain chronification, especially for orofacial pain. We next elaborate on the corticolimbic circuitry and underlying mechanisms that determine the transition to chronic pain. Given this knowledge, we advance a new mechanistic definition of chronic pain and discuss the clinical implications of this new definition as well as novel therapeutic potentials suggested by these advances.